Follicular Cell-Derived Thyroid Carcinomas: Current Status and Future Prospects

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Causes, Screening and Diagnosis".

Deadline for manuscript submissions: closed (30 June 2021) | Viewed by 25870

Special Issue Editors


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Guest Editor
Department of Pathology, Jewish General Hospital, McGill University, Montréal, QC, Canada
Interests: thyroid cancer; papillary thyroid carcinoma; poorly differentiated thyroid carcinoma; anaplastic thyroid carcinoma; molecular pathology; cytology; fine needle aspiration; histopathology
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Synlab Pathology, Lausanne, Switzerland
Interests: thyroid cancer; thyroid cythology; molecular pathology; thyroid carcinogenesis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Follicular cell-derived thyroid cancers (FCDTC) are derived from the follicular cells in the thyroid gland, which are responsible for iodine uptake and thyroid hormone synthesis. FCDTC can be roughly classified into papillary thyroid cancer (80%–85%), including its numerous variants, follicular thyroid cancer (6%–10%), Hürthle (oncocytic) thyroid cancer (5%–10%), poorly differentiated thyroid cancer (1%–7%), and undifferentiated (anaplastic) thyroid cancer (<2%), and these usually have an excellent prognosis, with the exception of poorly understood and undifferentiated thyroid cancers. Within the last decade, there have been major advances in our knowledge of the biology of FCDTC, which have had a significant impact on the classification and the management of these tumors. This has been achieved mainly through the progress of next-generation sequencing technologies and the correlation of clinicopathologic and genomic characteristics of FCDTC. Recently, a subset of indolent papillary thyroid carcinoma, the encapsulated follicular variant, has been reclassified into a low-malignant potential neoplasm entitled “Non-invasive follicular neoplasm with papillary-like nuclear features” given its excellent prognosis. In this Special Issue, experts in this field will review the diagnostic criteria on cytology and on histology, genetic profile, clinicopathologic characteristics, molecular drivers, management, as well as prognostic and predictive factors in FCDTC.

Dr. Marc Pusztaszeri
Dr. Massimo Bongiovanni
Guest Editors

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Keywords

  • thyroid cancer
  • papillary thyroid carcinoma
  • poorly differentiated thyroid carcinoma
  • anaplastic thyroid carcinoma
  • NIFTP
  • molecular pathology
  • cytology
  • fine needle aspiration
  • histopathology

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Published Papers (6 papers)

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Research

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11 pages, 990 KiB  
Article
Clinical Significance of Tumor Size in Gross Extrathyroidal Extension to Strap Muscles (T3b) in Papillary Thyroid Carcinoma: Comparison with T2
by Joonseon Park, Il Ku Kang, Ja Seong Bae, Jeong Soo Kim and Kwangsoon Kim
Cancers 2022, 14(19), 4615; https://doi.org/10.3390/cancers14194615 - 23 Sep 2022
Cited by 1 | Viewed by 1627
Abstract
The purpose of the present study was to compare the risk of recurrence between T2 and T3b papillary thyroid carcinoma (PTC) and the effect of tumor size on survival in T3b disease. A total of 634 patients with PTC who underwent thyroid surgery [...] Read more.
The purpose of the present study was to compare the risk of recurrence between T2 and T3b papillary thyroid carcinoma (PTC) and the effect of tumor size on survival in T3b disease. A total of 634 patients with PTC who underwent thyroid surgery at a single center were retrospectively analyzed. Clinicopathological characteristics were compared according to the T category in the TNM staging system, with T3b divided into T3b-1 (tumor size, ≤2 cm) and T3b-2 (tumor size, 2–4 cm). Disease-free survival (DFS) and recurrence risk were compared between T2, T3b, T3b-1, and T3b-2. Tumor size was significantly larger in T2 than in T3b. A significant difference in recurrence was observed between T2 and T3b-2 but not between T2 and T3b-1. T3b-2 was identified as a significant risk factor for PTC recurrence. A significant difference in the DFS curve was observed between T2 and T3b-2. However, no significant differences in survival were observed between T2 and T3b or T3b-1. These results indicate that the prognostic impact of T3b may vary depending on tumor size. Further studies are required to determine the need for T classifications that account for tumor size and gETE invasion of the strap muscles. Full article
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11 pages, 900 KiB  
Article
Central Lymph Node Ratio Predicts Recurrence in Patients with N1b Papillary Thyroid Carcinoma
by Il Ku Kang, Kwangsoon Kim, Joonseon Park, Ja Seong Bae and Jeong Soo Kim
Cancers 2022, 14(15), 3677; https://doi.org/10.3390/cancers14153677 - 28 Jul 2022
Cited by 4 | Viewed by 1604
Abstract
The lymph node ratio (LNR) indicates the number of metastatic lymph nodes (LNs) to the total number of LNs. The prognostic value of LNR in papillary thyroid carcinoma (PTC) and other solid tumors is known. This study aimed to investigate the relationship between [...] Read more.
The lymph node ratio (LNR) indicates the number of metastatic lymph nodes (LNs) to the total number of LNs. The prognostic value of LNR in papillary thyroid carcinoma (PTC) and other solid tumors is known. This study aimed to investigate the relationship between LNR and disease-free survival (DFS) in patients with PTC with lateral LN metastases (N1b PTC). A total of 307 patients with N1b PTC who underwent total thyroidectomy and therapeutic central and lateral LN dissection were retrospectively analyzed. The DFS and recurrence risk in the patients with LNR, central-compartment LNR (CLNR), and lateral-compartment LNR (LLNR) were compared. The mean follow-up duration was 93.6 ± 19.9 months. Eleven (3.6%) patients experienced recurrence. Neither LNR nor LLNR affected the recurrence rate in our analysis (p = 0.058, p = 0.106, respectively). However, there was a significant difference in the recurrence rates between the patients with low and high CLNR (2.1% vs. 8.8%, p = 0.017). In the multivariate analysis, CLNR ≥ 0.7 and perineural invasion were independent predictors of tumor recurrence. High CLNR was associated with an increased risk of recurrence, and was shown to be a significant predictor of prognosis in patients with N1b PTC. Full article
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15 pages, 1254 KiB  
Article
Is Gross Extrathyroidal Extension to Strap Muscles (T3b) Only a Risk Factor for Recurrence in Papillary Thyroid Carcinoma? A Propensity Score Matching Study
by Yongseon Kim, Yong-Seok Kim, Ja Seong Bae, Jeong Soo Kim and Kwangsoon Kim
Cancers 2022, 14(10), 2370; https://doi.org/10.3390/cancers14102370 - 11 May 2022
Cited by 3 | Viewed by 1798
Abstract
The presence of extrathyroidal extension (ETE) is associated with locoregional recurrence and distant metastases in papillary thyroid carcinoma (PTC). This study was designed to compare the recurrence risk between minimal ETE (mETE) and gross ETE (gETE) in patients with PTC using propensity score [...] Read more.
The presence of extrathyroidal extension (ETE) is associated with locoregional recurrence and distant metastases in papillary thyroid carcinoma (PTC). This study was designed to compare the recurrence risk between minimal ETE (mETE) and gross ETE (gETE) in patients with PTC using propensity score matching. In this study, 4452 patients with PTC who underwent thyroid surgery in a single center were retrospectively analyzed, and clinicopathological characteristics were compared according to the ETE status. Disease-free survival (DFS) and recurrence risk were compared between mETE and gETE after propensity score matching. The mean follow-up duration was 122.7 ± 22.5 months. In multivariate analysis, both mETE and gETE were not associated with recurrence risk before propensity score matching (p = 0.154 and p = 0.072, respectively). After propensity score matching, no significant difference in recurrence rates was observed between the two groups (p = 0.668). DFS of the gETE group did not significantly differ from that of the mETE group (log-rank p = 0.531). This study revealed that both mETE and gETE are not independent risk factors for the risk of recurrence in PTC. Our findings suggest that gETE invading strap muscles only might not be associated with worse oncological outcomes in PTC. Full article
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16 pages, 1630 KiB  
Article
Clinicopathological Features as Prognostic Predictors of Poor Outcome in Papillary Thyroid Carcinoma
by Antónia Afonso Póvoa, Elisabete Teixeira, Maria Rosa Bella-Cueto, Miguel Melo, Maria João Oliveira, Manuel Sobrinho-Simões, Jorge Maciel and Paula Soares
Cancers 2020, 12(11), 3186; https://doi.org/10.3390/cancers12113186 - 29 Oct 2020
Cited by 24 | Viewed by 3210
Abstract
Papillary thyroid cancer (PTC) has an indolent nature and usually excellent prognosis. Some PTC clinicopathological features may contribute to the development of aggressive metastatic disease. In this work, we want to evaluate PTC clinicopathological features that are presurgical prognostic predictors of patients’ outcomes [...] Read more.
Papillary thyroid cancer (PTC) has an indolent nature and usually excellent prognosis. Some PTC clinicopathological features may contribute to the development of aggressive metastatic disease. In this work, we want to evaluate PTC clinicopathological features that are presurgical prognostic predictors of patients’ outcomes and find which indicators are more adequate for tailoring surgical procedures and follow-up. We studied a series of 241 PTC patients submitted to surgery. All patients’ files and histological tumor samples were reviewed. The 8th edition AJCC/UICC (American Joint Committee on Cancer/Union for International Cancer) Controlstaging system and the 2015 American Thyroid Association risk stratification system were used. Total thyroidectomy was performed in 228 patients, lymphadenectomy in 28 patients. Gross extrathyroidal extension (ETE) was present in 10 patients and 31 tumor resection margins were incomplete. Cervical lymph node metastases (LNMs) were present in 34 patients and distant metastases at diagnosis in four patients. In multivariate analysis, male gender (OR = 15.4, p = 0.015), venous invasion (OR = 16.7, p = 0.022), and lateral compartment LNM (OR = 26.7, p = 0.004) were predictors of mortality; psammoma bodies (PBs) (OR = 4.5, p = 0.008), lymph vessel invasion (OR = 6.9, p < 0.001), and gross ETE (OR = 16.1, p = 0.001) were predictors of structural disease status; male gender (OR = 2.9, p = 0.011), lymph vessel invasion (OR = 2.8, p = 0.006), and incomplete resection margins (OR = 4.6, p < 0.001) were predictors of recurrent/persistent disease. Our study supports that the factors helping to tailor patient’s surgery are male gender, presence of PBs, gross ETE, and lateral compartment LNM. Together with pathological factors, lymph vessel invasion, venous invasion, necrosis, and incomplete surgical resection, should be taken into consideration regarding treatment and follow-up of patients. Full article
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8 pages, 213 KiB  
Article
Are Bethesda III Thyroid Nodules More Aggressive than Bethesda IV Thyroid Nodules When Found to Be Malignant?
by Sena Turkdogan, Marc Pusztaszeri, Veronique-Isabelle Forest, Michael P. Hier and Richard J. Payne
Cancers 2020, 12(9), 2563; https://doi.org/10.3390/cancers12092563 - 9 Sep 2020
Cited by 4 | Viewed by 13811
Abstract
The Bethesda classification system for thyroid fine needle aspirate (FNA) is used to predict the risk of malignancy and to guide the management of thyroid nodules. We postulated that thyroid malignancies characterized as Bethesda III on FNA have more aggressive features than those [...] Read more.
The Bethesda classification system for thyroid fine needle aspirate (FNA) is used to predict the risk of malignancy and to guide the management of thyroid nodules. We postulated that thyroid malignancies characterized as Bethesda III on FNA have more aggressive features than those classified as Bethesda IV. A retrospective chart review was performed to identify those who underwent thyroid surgery at a single tertiary hospital setting between 2015 and 2020. Associations between Bethesda category, molecular genetic test results, and histopathologic findings were examined. Out of 628 surgeries that were performed, 199 (54.2%) Bethesda III nodules and 216 (82.8%) Bethesda IV nodules were malignant. Of those that were malignant, 37 (18.6%) and 22 (10.2%) Bethesda III and Bethesda IV nodules showed aggressive features, respectively (p value = 0.014). There was a proportionally increased number of aggressive features in extra-thyroidal extension, lymph nodes metastasis, and all aggressive subtypes of papillary thyroid cancer in the Bethesda III category. Although Bethesda IV nodules are much more likely to be malignant (p value = 0.002), our study suggests that Bethesda III nodules that are resected are more likely to have aggressive features than Bethesda IV nodules, with a statistically significant increase in the solid variant of papillary thyroid cancer and lymph node metastasis. Full article

Review

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9 pages, 288 KiB  
Review
Papillary Thyroid Carcinoma with Desmoid-Type Fibromatosis: Review of Published Cases
by Abdallah Roukain, Stefano La Rosa, Massimo Bongiovanni, Marie Nicod Lalonde, Valérie Cristina, Michael Montemurro, Stephane Cochet, Alexandra Luquain, Peter A. Kopp and Gerasimos P. Sykiotis
Cancers 2021, 13(17), 4482; https://doi.org/10.3390/cancers13174482 - 6 Sep 2021
Cited by 6 | Viewed by 2946
Abstract
Desmoid-type fibromatosis (DTF) is a very rare variant of papillary thyroid carcinoma (PTC). It is essentially a dual tumor with a component of classical PTC with malignant epithelial proliferation (BRAF-mutated) and another component of mesenchymal proliferation (CTNNB1-mutated). We conducted [...] Read more.
Desmoid-type fibromatosis (DTF) is a very rare variant of papillary thyroid carcinoma (PTC). It is essentially a dual tumor with a component of classical PTC with malignant epithelial proliferation (BRAF-mutated) and another component of mesenchymal proliferation (CTNNB1-mutated). We conducted a literature review on PTC-DTF. In total, 31 articles were identified, that together reported on 54 patients. The mean age was 47 years, with a 2.2:1 female predominance. No ultrasound features were found to be helpful in differentiating PTC-DTF from other PTC variants. Of the 43 cases that reported histological details, 60% had locally infiltrative disease (T3b or T4). Around 48% had cervical lymph node metastases, but none had distant metastases. While PTC-DTF may be locally more aggressive than classic PTC, its overall behavior is similar and can include extrathyroidal extension and lymph node metastases, which may contain a stromal component and show extranodal invasion. The mainstay of treatment for PTC-DTF is surgery, and the DTF component is not expected to be sensitive to radioactive iodine. External radiotherapy, non-steroidal anti-inflammatory drugs, tyrosine kinase inhibitors and chemotherapy have also been used in selected cases. Due to the rarity of these tumors and the lack of specific treatment guidelines, management should be discussed in a multidisciplinary team. Full article
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